Intact PSA Free PSA

A DIAGNOSTIC BLOOD TEST FOR DETECTING THE RISK OF

AGGRESSIVE PROSTATE CANCER

PhysicianInformation

Intact PSA Free PSA

WHY USE THE 4KSCORE TEST?4Kscore Test determines the patient's risk for aggressive prostate cancer

• Two US based, prospective validation studies, including a 2017 study performed at Veterans Health Administration facilities involving a predominantly African American population, resulted in combined sensitivity of 94%, Negative Predictive Value (NPV) of 95% for the detection of Gleason 7 or higher (aggressive prostate cancer), with potential reduction of prostate biopsies of 32% when the 4Kscore Test at 7.5% cutoff was used. Both studies also demonstrated that the 4Kscore Test at 7.5% cutoff did not miss any Gleason 8 and higher on biopsy.1,2

• Two observational studies, using retrospective banked serum samples that were evaluated in over 4,000 subjects, show the long‐term, 15-20 years prediction of prostate cancer metastasis and death in men with elevated PSA3,4

• 4Kscore Test is included in the current US and European prostate cancer early detection guidelines5,6

• Over 200,000 4Kscore tests have been performed in the US

Risk of aggressive prostate cancer (%)

ResultComponentsTotal PSAFree PSAIntact PSAhK2 Prior Biopsy StatusAgeDRE (optional)

Proprietary to OPKO Algorithm

WHAT IS THE 4KSCORE TEST?4Kscore Test incorporates measurements of four kallikrein biomarkers and clinical information of a man in a validated assessment algorithm to detect the risk of aggressive prostate cancer on prostate biopsy

• Assesses the risk of aggressive prostate cancer following an abnormal PSA or DRE

� Provides the % risk of Gleason 7 or higher cancer if a prostate biopsy were performed

� Avoids or delays unnecessary prostate biopsy

� Prompts early intervention for men at elevated risk

Intact PSA Free PSA

4Kscore AccuracyNear-perfect calibration of 4Kscore risk assessments for aggressive prostate cancer and prostate biopsy results1

WHEN TO USE THE 4KSCORE TEST?

Patient management should be based on clinical judgment. Other clinical information (health status, medical history, family history of prostate cancer, PSA history, etc.), along with the 4Kscore Test result, should be considered in the shared decision making process.

% H

IGH

GRAD

E CA

NCER

ON

BIOP

SY

% 4Kscore TEST

AUC = 0.82

n = 1,012

100

80

60

40

20

0

0 20 40 60 80 100

LEGEND

Correlation of 4Kscore to prostate biopsy results

95% confidence interval

Perfect correlation

Abnormal PSA or DRE

Biopsy Naïve

or

Prior Negative Biopsy

Consider Biopsy or MRI

Routine Follow up

Elevated risk

Low risk

Intact PSA Free PSA

4KSCORE TEST IS NOT INDICATED IN MEN WITH:• Previous diagnosis of prostate cancer

• Digital Rectal Exam (DRE) performed within 96 hours before blood draw

• Use of 5-alpha reductase medication within previous 6 months

• Prostate procedure within the last 6 months

REFERENCES1. Parekh et al. A multi-institutional prospective trial in the USA confirms that the 4Kscore accurately identifies men with high-grade prostate cancer. Eur Urol.

2015;68(3):464-470.2. Punnen et al. A multi-institutional prospective trial confirms noninvasive blood test maintains predictive value in African American men. J Urol. 2018;199(6);1459-1463.3. Sjoberg et al. Twenty-year risk of prostate cancer death by midlife prostate-specific antigen and a panel of four kallikrein markers in a large population-based cohort of

healthy men. Eur Urol. 2018;73(6):941-948.4. Stattin et al. Improving the Specificity of Screening for Lethal Prostate cancer using prostate-specific antigen and a panel of kallikrein markers: a nested case-control

study. Eur Urol. 2015;68(2):207-213.5. National Comprehensive Cancer Network (NCCN). Prostate Cancer Early Detection (Version 1.2019). https://www.nccn.org/professionals/physician_gls/pdf/prostate_

detection.pdf 6. European Association of Urology (EAU). Guidelines on Prostate Cancer (Version 3.2016). https://uroweb.org/wp-content/uploads/EAU-Guidelines-Prostate-Cancer-2016.pdf

4Kscore Predictive ValueThe 4Kscore Test can stratify men and predict distant prostate cancer mortality3

Test Performed by BioReference Laboratories, Inc., an OPKO Health, Inc. Company© 2019 OPKO HEALTH, INC., ALL RIGHTS RESERVED. 200798 V1 04/19

The ordering and treating clinician should ensure that any and all testing ordered on behalf of his/her patients is reasonable and medically necessary.

Age enrolled 60–73, with a PSA of 2ng/ml at baseline would have 1.7% and 13% risks of death in 15 years, due to prostate cancer in the 4Kscore <7.5% and 4Kscore ≥7.5% respectively.3

4Kscore ≥7.5%4Kscore <7.5%

RISK

OF

PROS

TATE

CAN

CER

MOR

TALI

TY

YEARS SINCE BLOOD DRAW

0%

5%

10%

15%

20%

25%

0

54% of men PSA ≥2 ng/mL

46% of men PSA ≥2 ng/mL

5 10 15 20

n = 1,822

0.0% Risk5 years

0.6% Risk10 years